Thiazole derivatives

ABSTRACT

The invention provides thiazole derivatives of the general formula I: ##STR1## or an acid-addition salt or metal salt complex thereof, in which R represents an optionally substituted phenyl group; R 1  represents a hydrogen atom or an optionally substituted alkyl or phenyl group; R 2  represents a hydrogen atom or an optionally substituted akyl, alkylcarbonyl, alkenyl, cycloalkylcarbonyl or benzyl group; R 3  represents a hydrogen or halogen atom or a haloalkyl, alkoxy, haloalkoxy, alkylthio, hydroxyl, cyano, nitro or dialkylamino group; Y represents a group --CH 2  O-- or --CH 2  CH 2  -- and n is 0 or 1; processes for their preparation; compositions containing such compounds and their use as fungicides.

This invention relates to certain thiazole derivatives, a process fortheir preparation, compositions containing such compounds and their useas fungicides.

Tetrahedron Letters, 28(31), pp. 3585-3588, (1987) disoloses2-phenyl-1-(4-carboxyl-2-phenylthiazol-5-yl)propan-2-ol,2-phenyl-1-(4-diethylcarbamoyl)-2-methylthiazol-5-yl)propan-2-ol and1-phenyl-2-(4-diethylcarbamoyl-2-methylthiazol-5-yl)-ethanol. However,there is no indication that any of [; these compounds exhibit fungicidalactivity.

Can. J. Chem., 66 No. 7, pp. 1617-1624, (1988) disclosesbis(4-chlorophenyl)-(2-chlorothiazol-5-yl)-carbinol and furtherthiazol-5-yl carbinols of the formulae ##STR2## wherein, in formula (A),R'' represents a hydrogen or bromine atom and, either R' represents ahydrogen atom and R represents a hydrogen atom or a 4-chloro,3,4-dichloro, 4-methoxy or 4-trifluoromethyl substituent, or, both R'and R represent a 4-chloro substituent, and, in formula (B), Rrepresents a hydrogen atom or a methyl, methoxy or amino substituent. Invivo and in vitro tests indicated that some of the above compoundsexhibit a degree of fungicidal activity. However, it was noted that noneof the compounds was sufficiently active for economic use.

According to the present invention there is provided a compound of thegeneral formula ##STR3## or an acid-addition salt or metal salt complexthereof, in which R represents an optionally substituted phenyl group;R¹ represents a hydrogen atom or an optionally substituted alkyl orphenyl group; R² represents a hydrogen atom or an optionally substitutedalkyl, alkylcarbonyl, alkenyl, cycloalkylcarbonyl or benzyl group; R³represents a hydrogen or halogen atom or a haloalkyl, alkoxy,haloalkoxy, alkylthio, hydroxyl, cyano, nitro or dialkylamino group; Yrepresents a group --CH₂ O-- or --CH₂ CH₂ -- and n is 0 or 1.

When the compounds of this invention contain an alkyl or alkenylsubstituent group, this may be linear or branched and may contain up to12, preferably up to 6, carbon atoms. Cycloalkyl groups may contain 3 to8, preferably 3 to 6, carbon atoms.

When any of the foregoing substituents are designated as beingoptionally substituted, the substituent groups which are optionallypresent may be any one or more of those customarily employed in thedevelopment of pesticidal compounds, and/or the modification of suchcompounds to influence their structure/ activity, persistence,penetration or other property. Specific examples of such substituentsinclude, for example, halogen atoms, nitro, cyano, hydroxyl, alkyl,haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl,alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsulphinyl,alkylsulphonyl, carbamoyl and alkylamido groups. When any of theforegoing substituents represents or contains an alkyl substituentgroup, this may be linear or branched and may contain up to 12,preferably up to 6, and especially up to 4, carbon atoms.

It is preferred that R¹ is a phenyl group, substituted by 1 to 3halogen, especially chlorine or fluorine, atoms or C₁₋₄ alkyl,especially butyl, groups.

Preferably, R¹ represents a hydrogen atom, a C₁₋₁₂ alkyl, particularly aC₁₋₆ alkyl and especially a C₁₋ 4 alkyl, group or a phenyl group, eachgroup being optionally substituted by one or more substituents selectedfrom halogen atoms, nitro, cyano, hydroxyl, C₁₋₄ alkyl, C₁₋₄ haloalkyl,C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, amino, C₁₋₄ alkylamino, di-C₁₋₄alkylamino, formyl, C₁₋₄ alkoxycarbonyl and carboxyl groups.

It is also preferred that R² represents a hydrogen atom, a C₁₋₁₂ alkyl,particularly a C₁₋₆ alkyl and especially a C₁₋₄ alkyl, group, a C₂₋₁₂alkenyl, particularly a C₂₋₆ alkenyl and especially a C₂₋₄ alkenyl,group, a C₃₋₈ cycloalkylcarbonyl, particularly a C₃₋₆cycloalkylcarbonyl, group, or a benzyl group, each group beingoptionally substituted by one or more substituents selected from halogenatoms, nitro, cyano, hydroxyl, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy,C₁₋₄ haloalkoxy, amino, C₁₋₄ alkylamino, di-C₁₋₄ formyl, C₁₋₄alkoxycarbonyl and carboxyl groups.

Preferably, R³ represents a hydrogen or halogen atom.

A particularly preferred sub-group of compounds of formula I is that inwhich R represents a fluorophenyl, chlorophenyl, tert-butylphenyl,difluorophenyl or dichlorophenyl group; R¹ represents a hydrogen atom ora methyl, fluorophenyl, chlorophenyl or methylphenyl group; R²represents a hydrogen atom or an ethyl, allyl,dichloro-dimethylcyclopropylmethyl or chlorobenzyl group; and R³represents a hydrogen or chlorine atom.

It should also be appreciated that the compounds of formula I arecapable of existing as different optical isomers. The invention thusincludes both the individual isomers and mixtures of such isomers.

The present invention also provides a process for the preparation of acompound of formula I as defined above or an acid-addition salt or metalsalt complex thereof which comprises reacting a compound of the generalformula ##STR4## in which R^(3') represents a halogen atom or ahaloalkyl, alkoxy, haloalkoxy, alkylthio, hydroxyl, cyano, nitro ordialkylamino group, with a compound of the general formula ##STR5## inwhich R, R¹, Y and n are as defined above, in the presence of a base,such as butyl lithium or lithium diisopropylamide, to produce a compoundof formula I in which R² represents a hydrogen atom and R³ representsR^(3') ; if desired, reacting the compound of formula I so obtained witha reducing agent, such as zinc in acetic acid, to produce a compound offormula I in which R³ represents a hydrogen atom and/or, if desired,reacting the compound of formula I so obtained with a compound R^(2') X,in which R^(2') represents an optionally substituted alkyl,alkylcarbonyl, alkenyl, cycloalkylcarbonyl or benzyl group and Xrepresents a chlorine, bromine or iodine, preferably bromine, atom, inthe presence of a base, such as sodium hydride, to produce a compound offormula I in which R² represents R^(2') ; and, if desired, reacting acompound of formula I with a suitable acid or metal salt to form anacid-addition salt or metal salt complex thereof.

The process of the invention is conveniently carried out in the presenceof a solvent. Suitable solvents include ethers, such as tetrahydrofuran,and dimethylsulphoxide. Alternatively, the base may also act as thesolvent. The reaction is suitably carried out at a temperature of -100°C. to 150° C., the preferred reaction temperature being -80° C. to 120°C.

Compounds of formula II may be prepared from 2-aminothiazole (a knowncompound) using the procedure of K. Ganapathi and A. Venkataraman, Proc.Indian Acad. Sci., 1945, 22A, 343, 362 and conventional substitutionreactions.

Compounds of formula III may be prepared by reacting the correspondingketone with a trimethylsulphonium halide according to the procedure ofE. J. Corey and J. Chaykovsky, J.A.C.S., 1965, 87, 1353.

The compounds of general formula I have been found to have fungicidalactivity. Accordingly, the invention further provides a fungicidalcomposition which comprises a carrier and, as active ingredient, acompound of formula I or an acid-addition salt or metal salt complexthereof as defined above. A method of making such a composition is alsoprovided which comprises bringing a compound of formula I as definedabove, or an acid-addition salt or metal salt complex thereof, intoassociation with at least one carrier. Such a composition may contain asingle compound or a mixture of several compounds of the presentinvention. It is also envisaged that different isomers or mixtures ofisomers may have different levels or spectra of activity and thuscompositions may comprise individual isomers or mixtures of isomers.

A composition according to the invention preferably contains from 0.5 to95% by weight of active ingredient.

A carrier in a composition according to the invention is any materialwith which the active ingredient is formulated to facilitate applicationto the locus to be treated, which may for example be a plant, seed orsoil, or to facilitate storage, transport or handling. A carrier may bea solid or a liquid, including a material which is normally gaseous butwhich has been compressed to form a liquid, and any of the carriersnormally used in formulating fungicidal compositions may be used.

Suitable solid carriers include natural and synthetic clays andsilicates, for example natural silicas such as diatomaceous earths;magnesium silicates, for example talcs; magnesium aluminium silicates,for example attapulgites and vermiculites; aluminium silicates, forexample kaolinites, montmorillonites and micas; calcium carbonate;calcium sulphate; ammonium sulphate; synthetic hydrated silicon oxidesand synthetic calcium or aluminium silicates; elements, for examplecarbon and sulphur; natural and synthetic resins, for example coumaroneresins, polyvinyl chloride, and styrene polymers and copolymers; solidpolychlorophenols; bitumen; waxes, for example beeswax, paraffin wax,and chlorinated mineral waxes; and solid fertilisers, for examplesuperphosphates.

Suitable liquid carriers include water; alcohols, for exampleisopropanol and glycols; ketones, for example acetone, methyl ethylketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic oraraliphatic hydrocarbons, for example benzene, toluene and xylene;petroleum fractions, for example, kerosine and light mineral oils;chlorinated hydrocarbons, for example carbon tetrachloride,perchloroethylene and trichloroethane. Mixtures of different liquids areoften suitable.

Fungicidal compositions are often formulated and transported in aconcentrated form which is subsequently diluted by the user beforeapplication. The presence of small amounts of a carrier which is asurface-active agent facilitates this process of dilution. Thuspreferably at least one carrier in a composition according to theinvention is a surface-active agent. For example the composition maycontain at least two carriers, at least one of which is a surface-activeagent.

A surface-active agent may be an emulsifying agent, a dispersing agentor a wetting agent; it may be nonionic or ionic. Examples of suitablesurface-active agents include the sodium or calcium salts of polyacrylicacids and lignin sulphonic acids; the condensation products of fattyacids or aliphatic amines or amides containing at least 12 carbon atomsin the molecule with ethylene oxide and/or propylene oxide; fatty acidesters of glycerol, sorbitol, sucrose or pentaerythritol; condensates ofthese with ethylene oxide and/or propylene oxide; condensation productsof fatty alcohol or alkyl phenols, for example p-octylphenol orp-octylcresol, with ethylene oxide and/or propylene oxide; sulphates orsulphonates of these condensation products; alkali or alkaline earthmetal salts, preferably sodium salts, of sulphuric or sulphonic acidesters containing at least 10 carbon atoms in the molecule, for examplesodium lauryl sulphate, sodium secondary alkyl sulphates, sodium saltsof sulphonated castor oil, and sodium alkylaryl sulphonates such asdodecylbenzene sulphonate; and polymers of ethylene oxide and copolymersof ethylene oxide and propylene oxide.

The compositions of the invention may for example be formulated aswettable powders, dusts, granules, solutions, emulsifiable concentrates,emulsions, suspension concentrates and aerosols. Wettable powdersusually contain 25, 50 or 75% w of active ingredient and usually containin addition to solid inert carrier, 3-10% w of a dispersing agent and,where necessary, 0-10% w of stabiliser(s) and/or other additives such aspenetrants or stickers. Dusts are usually formulated as a dustconcentrate having a similar composition to that of a wettable powderbut without a dispersant, and may be diluted in the field with furthersolid carrier to give a composition usually containing 1/2-10% w ofactive ingredient. Granules are usually prepared to have a size between10 and 100 BS mesh (1.676-0.152 mm), and may be manufactured byagglomeration or impregnation techniques. Generally, granules willcontain 1/2-75% w active ingredient and 0-10% w of additives such asstabilisers, surfactants, slow release modifiers and binding agents. Theso-called "dry flowable powders" consist of relatively small granuleshaving a relatively high concentration of active ingredient.Emulsifiable concentrates usually contain, in addition to a solvent and,when necessary, co-solvent, 1-50% w/v active ingredient, 2-20% w/vemulsifiers and 0-20% w/v of other additives such as stabilisers,penetrants and corrosion inhibitors. Suspension concentrates are usuallycompounded so as to obtain a stable, non-sedimenting flowable productand usually contain 10-75% w active ingredient, 0.5-15% w of dispersingagents, 0.1-10% w of suspending agents such as protective colloids andthixotropic agents, 0-10% w of other additives such as defoamers,corrosion inhibitors, stabilisers, penetrants and stickers, and water oran organic liquid in which the active ingredient is substantiallyinsoluble; certain organic solids or inorganic salts may be presentdissolved in the formulation to assist in preventing sedimentation or asanti-freeze agents for water.

Aqueous dispersions and emulsions, for example compositions obtained bydiluting a wettable powder or a concentrate according to the inventionwith water, also lie within the scope of the invention. The saidemulsions may be of the water-in-oil or of the oil-in-water type, andmay have a thick `mayonnaise` like consistency.

The composition of the invention may also contain other ingredients, forexample other compounds possessing herbicidal, insecticidal orfungicidal properties.

Of particular interest in enhancing the duration of the protectiveactivity of the compounds of this invention is the use of a carrierwhich will provide a slow release of the fungicidal compounds into theenvironment of the plant which is to be protected. Such slow-releaseformulations could, for example, be inserted in the soil adjacent to theroots of a vine plant, or could include an adhesive component enablingthem to be applied directly to the stem of a vine plant.

The invention still further provides the use as a fungicide of acompound of the general formula I as defined above or an acid-additionsalt or metal salt complex thereof or a composition as defined above,and a method for combating fungus at a locus, which comprises treatingthe locus, which may be for example plants subject to or subjected tofungal attack, seeds of such plants or the medium in which such plantsare growing or are to be grown, with such a compound or composition.

The present invention is of wide applicability in the protection of cropplants against fungal attack. Typical crops which may be protectedinclude vines, grain crops such as wheat and barley, rice and tomatoes.The duration of protection is normally dependent on the individualcompound selected, and also a variety of external factors, such asclimate, whose impact is normally mitigated by the use of a suitableformulation.

The invention is further illustrated by the following examples.

EXAMPLE 1 Preparation of2-(2,4-dichlorophenyl)-1-(2-chlorothiazol-5-yl)propan-2-ol(R=2,4-dichlorophenyl; R¹ =methyl; R² =hydrogen; R³ =chlorine; n=0)

Butyl lithium (2.5 M, 12.5 ml) in hexane was added to a solution of2-chlorothiazole (3.6 g, 30 mmol) in tetrahydrofuran (100 ml) at -78° C.under an atmosphere of nitrogen. After 10 minutes, a solution of2-(2,4-dichlorophenyl)-2-methyloxirane (5.4 g, 26 mmol) intetrahydrofuran (40 ml) was added and the mixture was slowly allowed towarm to room temperature and then stirred for a further 3 hours. Waterwas added and the tetrahydrofuran was then evaporated under reducedpressure. The residue was extracted with ethyl acetate (2×300 ml) andthe combined organic extract was washed with saturated sodium chloridesolution and then dried. Flash chromatography of the residue on a silicagel column using ethyl acetate-petroleum ether as eluant gave2-(2,4-dichlorophenyl)-1-(2-chlorothiazol-5-yl)-propan-2-ol (6.4 g) as awhite solid, m.pt. 164° C.

Analysis: Calc: C: 44.7; H: 3.1; N: 4.3% ; Found: C: 45.2; H: 3.2; N:4.3%.

EXAMPLE 2 Preparation of2-(2,4-dichlorophenyl)-1-(thiazol-5-yl)propan-2-ol(R=2,4-dichlorophenyl; R¹ =methyl; R² =hydrogen; R³ =hydrogen; n=0)

The 2-(2,4-dichlorophenyl)-1-(2-chlorothiazol-5-yl)propan-2-ol (6.4 g)obtained in Example 1 was dissolved in acetic acid (80 ml) and themixture brought to reflux whereupon zinc dust (3.5 g) was added and themixture was stirred under reflux for a further 2 hours and then cooled.Dilute ammonium hydroxide solution was added until the reaction mixturewas basic and the mixture was then extracted into ethyl acetate (2×200ml). The combined extract was washed with brine (50 ml), dried and thenconcentrated under reduced pressure. Flash chromatography of the residueon a silica gel column using petroleum ether-ethyl acetate as eluantgave 2-(2,4-dichlorophenyl)-1-(thiazol-5-yl)propan-2-ol (3.2 g) as awhite solid, m.pt. 164° C.

Analysis: Calc: C: 50.0; H: 4.0; N: 4.9% , Found: C: 50.0; H: 3.8; N:4.9%.

EXAMPLE 3 Preparation of1-(2,4-dichlorophenyl)-1-ethoxy-2-(thiazol-5-yl)ethane(R=2,4-dichlorophenyl; R¹ =hydrogen; R² =ethyl; R³ =hydrogen; n™0)

Sodium hydride (0.2 g, 50%) was washed with dry petroleum ether,decanted and pumped dry.1-(2,4-dichlorophenyl)-2-(thiazol-5-yl)ethan-1-ol (0.9 g), prepared by aprocess analogous to that of Examples 1 and 2, was dissolved indimethylsulphoxide (25 ml) and the resultant solution was then added tothe sodium hydride. The resultant mixture was stirred at roomtemperature for 2 hours before ethyl bromide (lml) was added. After afurther hour, water was added and the resultant mixture was extractedinto ethyl acetate (2×200 ml). The combined organic extract was washedwith brine (50 ml), dried and the solvent evaporated to leave an oil.Flash chromatography of this oil on a silica gel column using 1:4 ethylacetate:petroleum ether as eluant gave1-(2,4-dichlorophenyl)-1-ethoxy-2-(thiazol-5-yl) ethane (1.0 g) as anoil.

Analysis: Calc: C: 51.66; H: 4.3; N: 4.6%; Found C: 51.8; H: 4.3; N:4.3%.

EXAMPLES 4 to 18

By processes similar to those described in Examples 1 to 3 above,further compounds according to the invention were prepared as detailedin Table I below. In this table, the compounds are identified byreference to formula I. Melting point and C,H,N analysis data for thecompounds of Examples 4 to 18 are given in Table IA below.

                                      TABLE I                                     __________________________________________________________________________    Example No.                                                                          R         R.sup.1 R.sup.2   R.sup.3                                                                          n Y                                     __________________________________________________________________________    4      4-fluorophenyl                                                                          2-fluorophenyl                                                                        H         H  0 --                                    5      4-fluorophenyl                                                                          4-fluorophenyl                                                                        H         H  0 --                                    6      4-fluorophenyl                                                                          4-chlorophenyl                                                                        H         H  0 --                                    7      4-chlorophenyl                                                                          H       CH.sub.2 CH.sub.3                                                                       H  1 CH.sub.2 O                            8      4-chlorophenyl                                                                          H       CH.sub.2 CHCH.sub.2                                                                     H  1 CH.sub.2 O                            9      4-chlorophenyl                                                                          4-chlorophenyl                                                                        H         H  0 --                                    10     4-chlorophenyl                                                                          4-methylphenyl                                                                        H         H  0 --                                    11     4-chlorophenyl                                                                          H       4-chlorobenzyl                                                                          H  1 CH.sub.2 O                            12     4-tert-butylphenyl                                                                      H       CH.sub.2 CH.sub.3                                                                       H  1 CH.sub.2 O                            13     4-tert-butylphenyl                                                                      H       CH.sub.2 CHCH.sub.2                                                                     H  1 CH.sub.2 O                            14     2,4-difluorophenyl                                                                      CH.sub.3                                                                              H         H  0 --                                    15     2,4-dichlorophenyl                                                                      H       H         H  0 --                                    16     2,4-dichlorophenyl                                                                      H       CH.sub.2 CHCH.sub.2                                                                     H  0 --                                    17     2,4-dichlorophenyl                                                                      H       4-chlorobenzyl                                                                          H  0 --                                    18A    2,4-dichlorophenyl                                                                      H                                                                                      ##STR6## H  0 --                                    18B    2,4-dichlorophenyl                                                                      H                                                                                      ##STR7## H  0 --                                    __________________________________________________________________________     NB. Examples 18A and 18B are different enantiomeric pairs of the same         compound.                                                                

                  TABLE IA                                                        ______________________________________                                        Exam-           Analysis (%)                                                  ple     M. pt.  C          H        N                                         No.     °C.                                                                            Calc   Found Calc Found Calc Found                            ______________________________________                                         4      153.3   64.3   64.3  4.1  4.2   4.4  4.3                               5      185.0   64.3   64.5  4.1  4.5   4.4  4.9                               6      151.8   61.2   61.1  3.9  3.9   4.2  4.0                               7              56.4   57.1  5.3  6.0   4.7  4.8                               8              58.2   59.8  5.7  5.9   4.5  4.5                               9      146.9   58.3   58.3  3.7  3.8   4.0  4.2                              10      146.0   65.6   65.7  4.8  5.0   4.2  4.7                              11              58.0   58.7  4.3  4.7   3.5  3.8                              12              67.7   67.9  7.8  8.1   4.3  4.4                              13              68.8   68.9  7.5  7.7   4.2  4.4                              14      130.3   56.5   56.5  4.3  4.5   5.5  5.6                              15       98.2   48.2   48.4  3.3  3.4   5.1  5.3                              16              53.5   53.5  4.2  4.3   4.5  4.6                              17              54.2   54.3  3.55 3.9   3.5  4.1                               18A            46.5   46.8  3.5  3.7   3.2  3.3                               18B            46.5   46.8  3.5  3.8   3.2  3.4                              ______________________________________                                    

EXAMPLE 19

The fungicidal activity of compounds of the invention was investigatedby means of the following tests.

(a) Direct Protectant Activity Against Vine Downy Mildew (PlasmoparaViticola; Pvp)

The test is a direct protectant one using a foliar spray. The lowersurfaces of leaves of whole vine plants (cv Cabernet Sauvignon) aresprayed with a solution of the test compound in 1:1 water/acetonecontaining 0.04% "TWEEN 20" (Trade Mark; a polyoxyethylene sorbitanester surfactant) using a moving track sprayer giving an applicationrate of 1 kg/ha and, after a subsequent 24 hours under normal glasshouseconditions, the lower surfaces of the leaves are inoculated by sprayingwith an aqueous solution containing 10⁴ zoosporangia/ml. The inoculatedplants are kept for 24 hours in a high humidity compartment, 5 daysunder normal glasshouse conditions and then returned for a further 24hours to high humidity. Assessment is based on the percentage of leafarea covered by sporulation compared with that on control leaves.

(b) Direct Protectant Activity Against Vine Grey Mould (BotrytisCinerea; Bcp)

The test is a direct protectant one using a foliar spray. The lowersurfaces of detached vine leaves (cv Cabernet Sauvignon) are sprayedwith the test compound at a dosage of lkg/ha using a track sprayer as in(a). 24 hours after spraying the leaves are inoculated with droplets ofaqueous suspension containing 10⁵ conidia/ml. After a further 5 days inhigh humidity the percentage of leaf area covered by disease isassessed.

(c) Activity against Wheat Leafspot (Leptosphaeria nodorum; Ln.)

The test is a direct therapeutic one, using a foliar spray. Leaves ofwheat plants (cv Mardler), at the single leaf stage, are inoculated byspraying with an aqueous suspension containing 1×10⁶ spores/ml. Theinoculated plants are kept for 24 hours in a high humidity compartmentprior to treatment. The plants are sprayed with a solutioin of the testcompound at a dosage of 1 kilogram of active material per hectare usinga track sprayer as described under (a). After drying, the plants arekept for 6-8 days at 20°-25° C. and moderate humidity, followed byassessment. Assessment is based on the density of lesions per leafcompared with that on leaves of control plants.

(d) Activity Against Barley Powdery Mildew (Erysiphe Graminis f.sp.hordei; Eg)

The test is a direct therapeutic one, using a foliar spray. Leaves ofbarley seedlings, (cv. Golden Promise) are inoculated by dusting withmildew conidia one day prior to treatment with the test compound. Theinoculated plants are kept overnight at glasshouse ambient temperatureand humidity prior to treatment. The plants are sprayed with the testcompound at a dosage of 1 kilogram of active material per hectare usinga track sprayer as described under (a). After drying, plants arereturned to a compartment at 20°-25° C. and moderate humidity for up to7 days, followed by assessment. Assessment is based on the percentage ofleaf area covered by sporulation compared with that on leaves of controlplants.

(e) Activity Against Wheat Brown Rust (Puccinia recondita; Pr)

The test is a direct protectant one using a foliar spray. Wheatseedlings (cv Brigand) are grown to the 1-11/2 leaf stage. The plantsare then sprayed with the test compound at a dosage of 1 kg/ha using atrack sprayer as described under (a). Test compounds are applied assolutions or suspensions in a mixture of acetone and water (50:50 v/v)containing 0.04% surfactant ("TWEEN 20"--Trade Mark).

18-24 hours after treatment, the seedlings are inoculated by sprayingthe plants from all sides with an aqueous spore suspension containingabout 10⁵ spores/ml For 18 hours after inoculation, the plants are keptin high humidity conditions at a temperature of 20°-22° C. Thereafter,the plants are kept in ambient glasshouse conditions, that is, inmoderate relative humidity and at a temperature of 20° C.

The disease is assessed 10 days after inoculation on the basis of thepercentage of the plant covered by sporulating pustules compared withthat on the control plants.

(f) Activity Against Rice Leaf Blast (Pyricularia oryzae Po)

The test is a direct therapeutic one using a foliar spray. The leaves ofrice seedlings (about 30 seedlings per pot) are sprayed with an aqueoussuspension containing 10⁵ spores/ml 20-24 hours prior to treatment withthe test compound. The inoculated plants are kept overnight in highhumidity and then allowed to dry before spraying with the test compoundat a dosage of 1 kilogram of active material per hectare using a tracksprayer as described under (a). After treatment the plants are kept in arice compartment at 25°-30° C. and high humidity. Assessments are made4-5 days after treatment and are based on the density of necroticlesions per leaf when compared with control plants.

(g) Activity Against Tomato Early Blight (Alternaria solani; As)

This test measures the contact prophylactic activity of test compoundsapplied as a foliar spray.

Tomato seedlings (cv Outdoor Girl) are grown to the stage at which thesecond true leaf is expanded. The plants are treated using a tracksprayer as described under (a). Test compounds are applied as solutionsor suspensions in a mixture of acetone and water (50:50 v/v) containing0.04% surfactant ("TWEEN 20"--Trade Mark).

One day after treatment the seedlings are inoculated by spraying theleaf upper surfaces with a suspension of A. solani conidia containing10⁴ spores/ml. For 3 days after inoculation plants are kept moist in aglasshouse compartment at or near 100% RH and 21° C. Thereafter plantsare kept under humid, but not saturated, conditions. Disease is assessed7 days after inoculation, based on the density and spread of lesions.

(h) Activity Against Wheat Eyespot In-vitro (Pseudocercosporellaherpotrichoides; PhI)

This test measures the in vitro activity of compounds against the funguscausing wheat eyespot.

The test compound is dissolved or suspended in acetone and is added tomolten half strength Potato Dextrose Agar to give a final concentrationof 100 ppm compound and 3.5% acetone. After the agar has set, plates areinoculated with 6 mm diameter plugs of agar/mycelium taken from a 14 dayold culture of P. herpotrichoides.

Plates are incubated at 20° C. for 12 days and radial growth from theinoculation plug is measured.

(i) Activity Against Fusarium In-vitro (Fusarium species; FsI)

This test measures the in vitro activity of compounds against a speciesof Fusarium that causes stem and root rots.

Compound is dissolved or suspended in acetone and added to molten halfstrength Potato Dextrose Agar to give a final concentration of 100 ppmcompound and 3.5% acetone. After the agar has set, plates are inoculatedwith 6 mm diameter plugs of agar and mycelium taken from a 7 day oldculture of Fusarium sp..

Plates are incubated at 20° C. for 5 days and radial growth from theplug is measured.

The extent of disease control in all the above tests is expressed as arating compared with either an untreated control or adiluent-sprayed-control, according to the criteria:

0=less than 50% disease control

1=about 50-80% disease control

2=greater than 80% disease control

The results of these tests are set out in Table II below:

                  TABLE 2                                                         ______________________________________                                        Compound                                                                      Example No.                                                                             Pvp    Bcp    Ln  Eg  Pr  Po  As  PhI  FsI                          ______________________________________                                        1                       2               1                                     2                2      2   2           2   2    1                            3         1             2   2       1   2   2    2                            4                           2       1   2   2    1                            5         1             2   2           1   2    1                            6         2             2   2   2   1   2   2    1                            7                       2   1   1   1   1   2    1                            8         1             2   2   1   1       1    1                            9         2      2      1   2   2       2   2    1                            10                          2   2           1    1                            11        1             1   2                                                 12        1                 2   2       1   1    1                            13        1             1   2           1                                     14                          2       1       2    2                            15        1      1      2   2               1    2                            16        1             2   2       1   1   2    2                            17                      1   2               1                                 18        1             1                                                     19        1                                                                   ______________________________________                                    

I claim:
 1. A compound of the general formula ##STR8## or an acid-addition salt or metal salt complex thereof, in which R represents an optionally substituted phenyl group; R¹ represents a hydrogen atom or an optionally substituted C₁₋₁₂ alkyl or phenyl group; R² represents a hydrogen atom or an optionally substituted C₁₋₁₂ alkyl, C₁₋₁₂ alkylcarbonyl, C₂₋₁₂ alkenyl, C₃₋₈ cycloalkylcarbonyl or benzyl group; R³ represents a hydrogen or halogen atom or a C₁₋₂ haloalkyl, C₁₋₁₂ alkoxy, C₁₋₁₂ haloalkoxy, C₁₋₁₂ alkylthio, hydroxyl, cyano, nitro or di-C₁₋₁₂ alkylamino group; Y represents a group --CH₂ O-- or --CH₂ CH₂ -- and n is 0 or 1; said optional substituents being selected from halogen atoms, nitro, cyano, hydroxyl, C₁₋₁₂ alkyl, C₁₋₁₂ haloalkyl, C₁₋₁₂ alkoxy, C₁₋₁₂ haloalkoxy, amino, C₁₋₁₂ alkylamino, di-C₁₋₁₂ alkylamino, formyl, C₁₋₁₂ alkoxycarbonyl, carboxyl, C₁₋₁₂ alkanoyl, C₁₋₁₂ alkylthio, C₁₋₁₂ alkylsulphinyl, C₁₋₁₂ alkylsulphonyl, carbamoyl and C₁₋₁₂ alkylamido groups.
 2. A compound according to claim 1 in which R represents a phenyl group substituted by 1 to 3 halogen atoms or C₁₋₄ alkyl groups.
 3. A compound according to claim 1 in which R¹ represents a hydrogen atom, a C₁₋₆ alkyl group or a phenyl group, each group being optionally substituted by one or more substituents selected from halogen atoms, nitro, cyano, hydroxyl, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, amino, C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, formyl, C₁₋₄ alkoxycarbonyl and carboxyl groups.
 4. A compound according to claim 1 in which R² represents a hydrogen atom, a C₁₋₆ alkyl group, a C₂₋₆ alkenyl group, a C₃₋₆ cycloalkyl carbonyl group or a benzyl group, each group being optionally substituted by one or more substituents selected from halogen atoms, nitro, cyano, hydroxyl, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, amino, C₁₋₄ alkylamino, di-C₁₋₄ alkylamino, formyl, C₁₋₄ alkoxycarbonyl and carboxyl groups.
 5. A compound according to claim 1 in which R³ represents a hydrogen or halogen atom.
 6. A compound according to claim 1 in which R³ represents a fluorophenyl, chlorophenyl, tert-butylphenyl, difluorophenyl or dichlorophenyl group; R¹ represents a hydrogen atom or a methyl, fluorophenyl, chlorophenyl or methylphenyl group; R² represents a hydrogen atom or an ethyl, allyl, dichloro-dimethylcyclopropylmethyl or chlorobenzyl group; and R³ represents a hydrogen or chlorine atom.
 7. A fungicidal composition which comprises a carrier and, as active ingredient, a compound of formula I or an acid-addition salt or metal salt complex thereof as defined in claim
 1. 8. A method of combating fungus at a locus which comprises treating the locus with a compound of formula I, or an acid-addition salt or metal complex thereof, as defined in claim
 1. 9. A method of combating fungus at a locus which comprises treating the locus with a composition as defined in claim
 7. 